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Discovery And Development Of Nucleoside And Nucleotide Reverse-transcriptase Inhibitors
Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs and NtRTIs) began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug resistance, Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs. History In the summer of 1981 the acquired immunodeficiency syndrome (AIDS) was first reported. Two years later the etiological link to AIDS, the human immunodeficiency virus (HIV) was identified. Since the identification of HIV the development of effective antiretrovi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building blocks of DNA and RNA. List of nucleosides and corresponding nucleobases ''This list does not include modified nucleobases and the corresponding nucleosides'' Each chemical has a short symbol, useful when the chemical family is clear from the context, and a longer symbol, if further disambiguation is needed. For example, long nucleobase sequences in genomes are usually described by CATG symbols, not Cyt-Ade-Thy-Gua (see '' Nucleic acid sequence § Notation''). Sources Nucleosides can ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lamivudine
Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet. Common side effects include nausea, diarrhea, headaches, feeling tired, and cough. Serious side effects include liver disease, lactic acidosis, and worsening hepatitis B among those already infected. It is safe for people over three months of age and can be used during pregnancy. The medication can be taken with or without food. Lamivudine is a nucleoside reverse transcriptase inhibitor and works by blocking the HIV reverse transcriptase and hepatitis B virus polymeras ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Subunit
In structural biology, a protein subunit is a polypeptide chain or single protein molecule that assembles (or "''coassembles''") with others to form a protein complex. Large assemblies of proteins such as viruses often use a small number of types of protein subunits as building blocks. A subunit is often named with a Greek or Roman letter, and the numbers of this type of subunit in a protein is indicated by a subscript. For example, ATP synthase has a type of subunit called α. Three of these are present in the ATP synthase molecule, leading to the designation α3. Larger groups of subunits can also be specified, like α3β3-hexamer and c-ring. Naturally occurring proteins that have a relatively small number of subunits are referred to as oligomeric.Quote: ''Oligomer molecule: A molecule of intermediate relative molecular mass, the structure of which essentially comprises a small plurality of units derived, actually or conceptually, from molecules of lower relative molecula ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life. Amino acids can be classified according to the locations of the core structural functional groups ( alpha- , beta- , gamma- amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type ( aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on Earth and its emergence. Amino acids are formally named by the IUPAC- IUBMB Joint Commi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heteroduplex
A heteroduplex is a double-stranded ( duplex) molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from ''different'' sources, such as from different homologous chromosomes or even from different organisms. One such example is the heteroduplex DNA strand formed in hybridization processes, usually for biochemistry-based phylogenetic analyses. Another is the heteroduplexes formed when non-natural analogs of nucleic acids are used to bind with nucleic acids; these heteroduplexes result from performing antisense techniques using single-stranded peptide nucleic acid, 2'-O-methyl phosphorothioate or Morpholino oligos to bind with RNA. Meiotic recombination can be initiated by a double-strand break (DSB) in DNA. The 5’ ends of the break are degraded, leaving long 3’ overhangs of several hundred nucleotides (see Figure). One of these 3’ single stranded DNA segments then invades a homologous sequence on the homologous chr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ribonuclease H
Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes. The family is divided into evolutionarily related groups with slightly different substrate preferences, broadly designated ribonuclease H1 and H2. The human genome encodes both H1 and H2. Human ribonuclease H2 is a heterotrimeric complex composed of three subunits, mutations in any of which are among the genetic causes of a rare disease known as Aicardi–Goutières syndrome. A third type, closely related to H2, is found only in a few prokaryotes, whereas H1 and H2 occur in all domains of life. Additionally, RNase H1-like retroviral ribonuclease H domains occur in multidomain reverse transcriptase proteins, which are encoded by retroviruses such as HIV and are required for viral repl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences (see non-coding DNA), and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondrial DNA, mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplast DNA, chloroplasts with a chloroplast genome. The study of the genome is called genomics. The genomes of many organisms have been Whole-genome sequencing, sequenced and various regions have been annotated. The first genome to be sequenced was that of the virus φX174 in 1977; the first genome sequence of a prokaryote (''Haemophilus influenzae'') was published in 1995; the yeast (''Saccharomyces cerevisiae'') genome was the first eukaryotic genome to be sequenced in 1996. The Human Genome Project ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell (biology)
The cell is the basic structural and functional unit of all life, forms of life. Every cell consists of cytoplasm enclosed within a Cell membrane, membrane; many cells contain organelles, each with a specific function. The term comes from the Latin word meaning 'small room'. Most cells are only visible under a light microscope, microscope. Cells Abiogenesis, emerged on Earth about 4 billion years ago. All cells are capable of Self-replication, replication, protein synthesis, and cell motility, motility. Cells are broadly categorized into two types: eukaryotic cells, which possess a Cell nucleus, nucleus, and prokaryotic, prokaryotic cells, which lack a nucleus but have a nucleoid region. Prokaryotes are single-celled organisms such as bacteria, whereas eukaryotes can be either single-celled, such as amoebae, or multicellular organism, multicellular, such as some algae, plants, animals, and fungi. Eukaryotic cells contain organelles including Mitochondrion, mitochondria, which ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Nucleus
The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, no nuclei, and a few others including osteoclasts have Multinucleate, many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support. The cell nucleus contains nearly all of the cell's genome. Nuclear DNA is often organized into multiple chromosomes – long strands of DNA dotted with various proteins, such as histones, that protect and organize the DNA. The genes within these chromosomes are Nuclear organization, structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Polymerase
In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using Base pair, base-pairing interactions or RNA by half ladder replication. A DNA polymerase from the thermophile, thermophilic bacterium, ''Thermus aquaticus'' (''Taq'') (Protein Data Bank, PDB]1BGX EC 2.7.7.7) is used in the polymerase chain reaction, an important technique of molecular biology. A polymerase may be template-dependent or template-independent. Polynucleotide adenylyltransferase, Poly-A-polymerase is an example of template independent polymerase. Terminal deoxynucleotidyl transferase also known to have template independent and template dependent activities. By function *DNA polymerase (DNA-directed DNA polymerase, DdDP) **Family A: DNA polymerase I; Pol POLG, γ, POLQ, θ, DNA polymer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Retroviruses
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus ''retro'' (backward). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds. Retroviruses have many subfamilies in three basic groups. * Oncoretroviruses (cancer-causing retroviruses) include human T-lymphotropic virus (HTLV) causing a type of leukemia in humans, and murine leuk ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
